VIENNA, Va. ( TheStreet) --If all goes as planned this summer, Cel-Sci ( CVM) will enroll the first of 800 patients in a phase III study of its experimental cancer drug Multikine. This pivotal study will compare treatment with Multikine plus the standard of care (surgery followed by chemotherapy/radiation) against the standard of care alone in patients with newly diagnosed head and neck cancer. The study hopes to show that treatment with Multikine plus standard of care can prolong survival by 10% compared with standard of care alone. Since survival is the gold standard for measuring benefit in cancer studies, a positive (and statistically significant) result from the study will go a long way towards helping Cel-Sci convince U.S. drug regulators to approve Multikine as a new treatment for head and neck cancer. On Tuesday, Cel-Sci CEO Geert Kersten spent most of his presentation slot at the BIO CEO & Investor Conference discussing the benefits of Multikine. He talked about data from phase II studies, which showed that treatment with Multikine led to complete responses (total tumor shrinkage) in 12% of head and neck cancer patients while other patients saw their tumors shrink by half. Most importantly, according to Kersten, treatment with Multikine in the phase II study improved overall survival by 33% compared with standard of care. The phase III study design exactly mimics that of the phase II study and only needs to show a 10% survival advantage, so the encouraging results observed in the earlier study bodes well for a positive result from the phase III study, said Kersten.
All this would be reason for optimism about Multikine if true. It's not. When Kersten speaks of Multikine, he's using half-truths and clever omissions of facts that make the drug appear much more effective than it really is. The claim of a 33% survival advantage in the phase II study is a particularly ginned-up figure. In fact, the Multikine phase II study, as published, was never designed to measure survival, nor did it do so. Cel-Sci used a scientific sleight of hand to derive the survival benefit, which by the way, has never been published in any medical journal, has never been peer reviewed by independent evaluators, nor has it ever been presented by an academically credentialed investigator at a major medical conference. Before I explain why Multikine's supposed 33% survival benefit should not be trusted, it's important to understand what the drug's primary phase II study did show. The phase II study of Multikine in head and neck cancer patients was published in May 2005 in the Journal of Clinical Oncology, arguably the most prestigious cancer-focused medical journal, published by the American Society of Clinical Oncology.
For those who want to look up the article, the citation is J Clin Oncol 23:3421-3432. Lead author Jozsef Timar. Conducted in Hungary, study investigators enrolled 19 previously untreated head and neck cancer patients. Each patient was injected with Multikine directly into and around the primary tumor plus an intravenous infusion of the chemotherapy drug cyclophosphamide. After three weeks of drug treatment, the 19 patients underwent surgery. In two patients out of the 19, or 10.5%, surgeons found no evidence of cancer in the resected tissue so they were deemed to be complete responders. In another two patients, the cancer shrunk by 50% so they were deemed partial responders. Therefore, the overall objective response rate was 21%, according to the study. Another four patients had minor tumor shrinkage, so the overall response rate was generously defined as 42%.
A few things to consider: First, this study was small, with only 19 patients enrolled, and only two of those patients, or 10.5%, reported a complete response.
Cel-Sci's math is screwy because in its press releases -- and in Kersten's pitch Tuesday -- the complete response rate is reported as 12%. That's inaccurate. But putting the bad math aside, notice how Kersten doesn't talk about only two patients reporting a complete response out of 19 patients -- a tiny sample size which makes drawing firm conclusions extremely difficult. Instead, Kersten says the complete response rate was 12% (actually 10.5%) because the percentage sounds a lot better without the context of the very small patient numbers. Second, these patients were not just treated with Multikine, they also received an infusion of cyclophosphamide, a chemotherapy drug known to have some tumor-shrinking effect in solid tumors. So, which drug caused the tumors to shrink in these patients? Was it Multikine? Was it cyclophosphamide? Or was it a combination of the two drugs? Unfortunately, the study wasn't designed to determine an answer. Third, and perhaps the most important point, is that the phase II study was not adequately controlled, meaning there was no enrollment of a comparator arm (i.e. patients treated only with cyclophosphamide or with a placebo), so that the benefit of Multikine could be objectively assessed. Instead, the investigators who ran this study used as a control 20 tumor specimens or samples taken from similar patients diagnosed with the same type of head and neck cancer. The only comparisons made in the study were to determine the effect that Multikine had on levels of certain immune cells infiltrating the tumors compared to the tumor samples not treated with Multikine.
The study's authors conclude, "The efficacy of this neoadjuvant treatment protocol for patients with advanced primary OSCC
head and neck cancer resulted in a marked reduction in tumor mass (in 42% of the patients) compared with baseline tumor measurements. These findings, taken together with our previous report, indicate that the LI Multikine neoadjuvant immunotherapy regimen for OSCC is a clinically viable approach to the management of OSCC. The results of larger efficacy trials (planned for the near future) may promote the introduction of LI into the current treatment protocols of OSCC." In part 2, I'll examine more closely why Cel-Sci's survival claim for Multikine is misleading.